PI3Kδ contributes to ER stress-associated asthma through ER-redox disturbances: the involvement of the RIDD–RIG-I–NF-κB axis

A pro-inflammatory protein induces asthma by stressing the endoplasmic reticulum (ER), the cell organelle responsible for protein folding. Drugs that block this stress could help treat asthma. A team led by Han-Jung Chae from Chonbuk National University in Jeonju, South Korea, examined the molecular effects of treating a mouse model of asthma with an aerosolized drug that inhibits phosphoinositol 3-kinase (PI3K), a protein involved in regulating immune mediators of inflammation. The researchers found that blocking PI3K activity led to lower levels of misfolded proteins and toxic free radicals in the ER. Consequently, cells lining the inside of the lungs released fewer pro-inflammatory signaling molecules, and the mice were less sensitive to asthma triggers. The authors conclude that inhalable PI3K inhibitors could help treat severe asthma.